Dataset Information

Cdc48’s interactions play a role in the cellular oxidative response in an aging-dependent manner

ABSTRACT: The cellular redox status has long been linked to different cellular functions, including protein quality control (PQC) and aging. The prominent molecular machine Cdc48 (p97/VCP in mammals) is one of the key players involved in PQC, shuttling misfolded proteins to degradation. Through a range of N-terminal interactions, Cdc48 recognizes ubiquitin-tagged proteins targeted for proteasomal degradation. Here, we show that yeast Cdc48 is a redox-switch protein, with oxidation of a thiol-switch in the conserved Cys115. Using redox mass spectrometry, we characterize the oxidation status of Cdc48’s cysteine residues in the shift from the early- to late-stationary stages. Cdc48’s interactome undergoes a proteomic-scale rearrangement following this oxidation and leads to an increased association with antioxidants. Moreover, we found that the oxidation status of Cys115 mediates the activity of Cdc48, its interaction with canonical cofactors such as Shp1, and subsequent involvement in maintaining protein homeostasis during chronological aging. This work not only points to a new thiol switch protein in the protein degradation pathway, but also defines new roles for Cdc48 in chronological aging.

INSTRUMENT(S): Q Exactive Plus, Q Exactive HF

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Meytal Radzinski

LAB HEAD: Dana Reichmann

PROVIDER: PXD045122 | Pride | 2025-05-28

REPOSITORIES: Pride

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Cdc48 plays a crucial role in redox homeostasis through dynamic reshaping of its interactome during early stationary phase.

Radzinski Meytal M Oppenheim Tal T Yogev Ohad O Levy Adi A Naomi Melamed-Book MB Kacen Assaf A Merbl Yifat Y Ravid Tommer T Reichmann Dana D

Redox biology 20250501

Most microbial cells on earth predominantly exist in non-proliferating, dormant conditions, such as the stationary state. The stationary phase is a crucial stage during the cellular lifespan, which requires homeostatic rewiring for long-term viability and rapid responses to environmental changes. Here, we show that entry to the stationary phase in yeast is accompanied by increased cytosolic and mitochondrial oxidation, imposing stress on the proteostasis network. We establish a functional link b ...[more]

PMID: 40359616

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			Action	DRS
	C115S_1_24h.raw	Raw
	C115S_1_48h.raw	Raw
	C115S_24h_1_allcell.raw	Raw
	C115S_24h_2_allcell.raw	Raw
	C115S_24h_3_allcell.raw	Raw